Stroke devastates the lives of several hundred thousand people and their families every year in the United States alone. Although technological advances continue to positively change the face of stroke, an enormous amount of research remains necessary to discover optimal prevention and treatment methods. The inability to precisely control where, when, and how strokes occur in human patients is a major obstacle to the effective investigation into mechanisms for better recovery after ischemia. This is especially important for reach training, a method commonly used to promote recovery in the many stroke victims who lose function in one arm after unilateral infarct. As such, in the current proposal is part of an ongoing effort to elucidate the best conditions for unilateral stroke recovery in rats. Ipsilesional reach training, or training the unaffected limb following sensorimotor infarct can negatively affect rats' ability to recover from the ischemic event in the affected limb during subsequent training. Further, ipsilesional training relatedly modulates neural recovery mechanisms in perilesion cortex. However, research has only begun to shed light on the mechanisms of ipsilesional training. For Aim 1, rats will receive unilateral chemical lesion in sensorimotor cortex controlling the preferred limb (a sham group will serve as controls). Next, rats will either undergo ipsilesional or no training, followed by rehabilitative training of the affected limb. Intracortical microstimulation (ICMS) mapping in motor cortex will be performed either after ipsilesional training or after rehabilitative training, for assessment of change in motor function. After ICMS, electron microscopic analyses will be used to examine differences in synapse measures in perilesion cortex. For Aim 2, the same methods and techniques mentioned above will be used, yet in contralesional motor cortex. Aim 3 will investigate whether changes in perilesion cortex are mediated by transcollosal inhibitory mechanisms in contralateral motor cortex by again delivering unilateral lesions to SMC controlling the preferred limb, training the ipsilesional forelimb, then injecting muscimol (a GABA agonist) or vehicle in contralesional motor cortex prior to rehabilitative training. Measures will be synonymous with the first two aims. This third aim will help clarify whether contralesional excitation is modifying perilesion recovery in real-time, or if changes in perilesion neural and behavioral function occurred only as a function of prior limb training. This series of experiments will isolate neural and behavioral mechanisms of ischemic recovery during reach training for continual refinement of existing medical techniques used in human patients with unilateral stroke. [unreadable] [unreadable] [unreadable]